KR850001174A - Chemical compound - Google Patents

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KR850001174A
KR850001174A KR1019840004474A KR840004474A KR850001174A KR 850001174 A KR850001174 A KR 850001174A KR 1019840004474 A KR1019840004474 A KR 1019840004474A KR 840004474 A KR840004474 A KR 840004474A KR 850001174 A KR850001174 A KR 850001174A
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헨리 브라운 토마스
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데비드 마틴 워터스
스미스 클라인 앤드 프렌취 라보라토리스 리미티드
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
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    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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Abstract

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Description

화학적 화합물Chemical compound

본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음As this is a public information case, the full text was not included.

Claims (22)

일반식(1)의 화합물이나 이들의 염을 제조하는 방법.The method of manufacturing the compound of General formula (1), and its salt. R0-(CH2)m-Y-(CH2)p-(NH)q R 0- (CH 2 ) m -Y- (CH 2 ) p- (NH) q 여기서,here, R0는 2-구아니디노티아졸-4-일이나 R1R2N(CH2)n-Z그룹이고, R1과 R2은 독립적으로 수소, C1-6알킬, 아릴(C1-6) 알킬, 헤테로아릴(C1-6) 알킬, C3-10싸이클로알킬, 하이드록시(C2-6) 알킬, 혹은 할로(C2-6) 알킬(여기에서 상기 하이드록시 및 할로그룹은 질소원소에 인접한 탄소원자에서 치환되지 않는다); 이거나 R1과 R2는 함께 -(CH2)q를 나타내며 여기에서 q는 4-7이고 5-8원의 포화환이 붙는 질소원자와 함께 형성되고; n은 1 내지 6의 정수이고; Z는 R1R2N(CH2)n그룹이 4-위치에 있는 2,5-푸라닐, 2,5-티에틸, 2,4-피리딜과 R1R2N(CH2)n그룹이 2-위치에 있는 2,4-티아졸릴이거나 1,3-이나 1,4-페닐렌이고; m은 1이거나; Z가 피리딜이나 페닐렌이면 m은 또한 0일 수도 있고; Y는 산소, 유황이나 메틸렌이거나, 혹은 Z는 푸라닐이며, 티에닐이나 티아졸릴 Y는 또한 한개의 결합일 수도 있고; p는 2,3 혹은 4이고; q는 0이거나 1이고; R3은 수소이거나 C1-6알킬이고, R4은 수소이거나 C1-6알카노일이며; 본 방법은 다음에 관한 것으로 구성되어 있다.R 0 is 2-guanidinothiazol-4-yl or R 1 R 2 N (CH 2 ) n -Z group, R 1 and R 2 are independently hydrogen, C 1-6 alkyl, aryl (C 1 -6 ) alkyl, heteroaryl (C 1-6 ) alkyl, C 3-10 cycloalkyl, hydroxy (C 2-6 ) alkyl, or halo (C 2-6 ) alkyl, wherein said hydroxy and halogroups Is not substituted at a carbon atom adjacent to a nitrogen element); Or R 1 and R 2 together represent — (CH 2 ) q wherein q is 4-7 and is formed together with a nitrogen atom to which a 5-8 membered saturated ring is attached; n is an integer from 1 to 6; Z is 2,5-furanyl, 2,5-thiethyl, 2,4-pyridyl and R 1 R 2 N (CH 2 ) n in which the R 1 R 2 N (CH 2 ) n group is 4-position The group is 2,4-thiazolyl in the 2-position or 1,3- or 1,4-phenylene; m is 1; M may also be 0 if Z is pyridyl or phenylene; Y is oxygen, sulfur or methylene, or Z is furanyl and thienyl or thiazolyl Y may also be one bond; p is 2, 3 or 4; q is 0 or 1; R 3 is hydrogen or C 1-6 alkyl, R 4 is hydrogen or C 1-6 alkanoyl; The method consists of the following. (a)식 (I)에서 q가 1인 화합물들의 경우, 식(II)의 화합물들과, 식(III)의 화합물을 반응시킴.(a) For compounds of q in formula (I), reacting compounds of formula (II) with compounds of formula (III). R6-(CH2)m-Y-(CH2)p-(NH)q R 6- (CH 2 ) m -Y- (CH 2 ) p- (NH) q (II)(II) 여기서, m,y,p 및 R3는 본원중 앞에서 정의한 바와같고, R6는 본원의 앞에서 정의한 바의 R0기이거나, 푸란-2-일 혹은 티엔-2-일기이며; R5는 보호된 아미노이고; Q는 아민으로 치환가능한 기임.Wherein m, y, p and R 3 are as defined above in the present application and R 6 is an R 0 group, furan-2-yl or thien-2-yl group as previously defined herein; R 5 is protected amino; Q is a group substitutable with an amine. (b) 식(I)에서 m이 1이고 Y가 황인 화합물인 경우, 식(IV)의 화합물과 식(V)의 화합물을 반응시킴.(b) reacting the compound of formula (IV) with the compound of formula (V) when m is 1 and Y is sulfur in formula (I). R6-CH2-L R 6 -CH 2 -L (IV)(IV) 여기서, R6,p,q, 및 R3는 본원의 앞에서 정의한 바와같고, R51은 임의로 보호된 아미노기이며, L은 티올이나 그 화학적 등가물로 치환가능한 부문임.Wherein R 6 , p, q, and R 3 are as previously defined herein, R 51 is an optionally protected amino group, and L is a substitutable moiety with thiol or a chemical equivalent thereof. (c) 식(I)에서 m이 1이고 Y가 황인 화합물인 경우, 식(VI)의 화합물이나 그 화학적 등가물과 식(VII)의 화합물을 반응시킴.(c) In the formula (I), when m is 1 and Y is sulfur, the compound of formula (VI) or its chemical equivalent and the compound of formula (VII) are reacted. R6CH2SH (VI) R 6 CH 2 SH (VI) 여기서, R6,P,q, R51및 R3는 본원중 앞에서 정의한 바와같고, L1은 티올이나 그 화학적 등가물로 치환 가능한 부문임.Wherein R 6 , P, q, R 51 and R 3 are as previously defined herein and L 1 is a substitutable moiety with thiol or its chemical equivalent. (d) 혹은 (c)의 화합물을 얻기 위해 식(VIII)의 화합물과 식(IX)의 화합물이나 그 화학적 등가물을 반응시킴.reacting a compound of formula (VIII) with a compound of formula (IX) or its chemical equivalents to obtain a compound of (d) or (c); 여기서, R6,m,y,p,q, 및 R3는 본원중 앞에서 정의한 바와같고, R52는 보호된 아미노이며 R7은 에스테르-형성기임; (e) 식(I)에서 z가 2,4-피리딜이고 m은 O, Y는 산소인 화합물의 경우, 식(X)의 화합물과 식(XI)의 화합물이나 반응할 수 있는 그 유도체를 반응시킴.Wherein R 6 , m, y, p, q, and R 3 are as previously defined herein, R 52 is a protected amino and R 7 is an ester-forming group; (e) In the formula (I), where z is 2,4-pyridyl and m is O and Y is oxygen, the compound of formula (X) and the compound of formula (XI) or a derivative thereof capable of reacting Reaction. 여기서 R1,R2,n,p,q,R3및 R51은 본원중 앞에서 정의한 바와같고, L2는 하이드록시나 그 등가물로 치환 가능한 기이다.Wherein R 1 , R 2 , n, p, q, R 3 and R 51 are as defined above in the present application, and L 2 is a group which may be substituted with hydroxy or an equivalent thereof. (f) 식(I)에서 z가 페닐렌, m이 o이고, y가 산소인 화합물의 경우, 식(XII)의 화합물이나 그 화학적 등가물과 식(XIII)의 화합물을 반응시킴.(f) In the case of a compound in which z is phenylene, m is o and y is oxygen in formula (I), the compound of formula (XII) or its chemical equivalent and the compound of formula (XIII) are reacted. 여기서, R1,R2,n,p,q,R3및 R51은 본원중 앞에서 정의한 바와 같으며, L3는 페놀이나 그 화학적 등가물로 치환 가능한 부분임.Wherein R 1 , R 2 , n, p, q, R 3 and R 51 are as defined above in the present application, and L 3 is a moiety that can be substituted with phenol or a chemical equivalent thereof. (g) 식(I)에서 R0가 R1R2N(CH2)-Z-인 화합물의 경우, 식(XIV)의 화합물을 변환시킴.(g) For compounds in which R 0 is R 1 R 2 N (CH 2 ) -Z- in formula (I), converts the compound of formula (XIV). 여기서, z,m,y,p,q,R3및 R51은 본원중 앞에서 정의한 바와같고, R8는 본원중 앞에서 정의한 R1R2N(CH2)n-기의 전조물임.Wherein z, m, y, p, q, R 3 and R 51 are as previously defined herein and R 8 is a precursor of the R 1 R 2 N (CH 2 ) n − group as previously defined herein. (h) 식(I)에서 q가 인 화합물들의 경우, 식(XV)의 화합물을 환원시킴.(h) in the case of compounds in which q in formula (I), reduces the compound of formula (XV). 여기서 1 m,y,p,R3및 R51은 본원중 앞에서 정의한 바와같고, R9는 본원중 앞에서 정의한 R8-Z-이거나 R0기이며, R10은 -CO-NH-이거나 -CH=N-기임; 그 밖에 다음이 필요함.Wherein 1 m, y, p, R 3 and R 51 are as previously defined herein, R 9 is an R 8 -Z- or R 0 group as previously defined herein and R 10 is -CO-NH- or -CH = N-term; In addition, (i) 식(I)에서 n이 1인 화합물을 생성시키기 위해 R6가 푸란-2-일이거나 티엔-2-일인 화합물을 만니히시약과 반응시킴.(i) reacting a compound wherein R 6 is furan-2-yl or thien-2-yl with Mannich reagent to produce a compound of formula (I) wherein n is 1. (ii) 보호된 아모니기를 아미노나 C1-6알카노일 아미노로 변환시킴.(ii) converting the protected amony group to amino or C 1-6 alkanoyl amino. (iii) 임의로 염을 형성함.(iii) optionally forming a salt. 여러가지 a)-d)의 어느 방법에 따라 시행될 경우 R1,R2,n 및 Z가 일반식(1)에서 정의한 바와같은 R0가 R1R2N(CH2)nZ-인 일반식(1)의 화합물이나 이들의 염을 제조하는 청구범위 제1항에 따른 제조방법.When carried out according to any of a) -d), R 1 , R 2 , n and Z are general, in which R 0 is R 1 R 2 N (CH 2 ) n Z- as defined in formula (1). A process according to claim 1 for producing a compound of formula (1) or a salt thereof. R4가 수소인 일반식(1)의 화합물이나 이들의 염을 제조하기 위한 청구범위 제1항이나 제2항에 따른 제조방법.A process according to claims 1 or 2 for producing compounds of formula (1) wherein R 4 is hydrogen or salts thereof. q가 1인 일반식(1)의 화합물이나 이들의 염을 제조하기 위한 청구범위 제1항내지 제3항중의 어느 하나에 따른 방법.The method according to any one of claims 1 to 3 for producing a compound of formula (1) wherein q is 1 or salts thereof. q가 1인 일반식(1)의 화합물이나 이들의 염을 제조하기 위한 청구범위 제1항내지 제3항중의 어느 하나에 따른 방법.The method according to any one of claims 1 to 3 for producing a compound of formula (1) wherein q is 1 or salts thereof. R3가 수소인 일반식(1)의 화합물이나 이들의 염을 제조하기 위한 청구범위 제1항내지 제5항중의 어느 하나에 따른 방법.The method according to any one of claims 1 to 5 for producing a compound of formula (1) or a salt thereof, wherein R 3 is hydrogen. R1과 R2가 다같이 q가 4-7인 -(CH2)q를 나타내는 일반식(1)의 화합물이나 이들의 염을 제조하기 위한 청구범위 제1항내지 제6항중의 어느 하나에 따른 방법.The compound of formula (1), wherein R 1 and R 2 together represent-(CH 2 ) q in which q is 4-7, or any one of claims 1 to 6 for the preparation of salts thereof. According to the method. R1R2N(CH2)n-Z-가 3피페리디노 메틸페닐인 일반식(1)의 화합물이나 이들의 염을 제조하기 위한 청구범위 제1항내지 제7항중의 어느 하나에 따른 방법.The process according to any one of claims 1 to 7 for preparing compounds of formula (1) wherein R 1 R 2 N (CH 2 ) n -Z- is 3piperidino methylphenyl or salts thereof. . 2-[3-(3-디메틸아미노메틸)페녹시)프로필아미노]-5-아미노-피리미딘-4-온 혹은 약제학상허용 가능한 염.2- [3- (3-dimethylaminomethyl) phenoxy) propylamino] -5-amino-pyrimidin-4-one or a pharmaceutically acceptable salt. 2-[3-(3-피페리디노메틸)페녹시)프로필]-5-아미노-피리미딘-4-온 혹은 약제학상허용 가능한 염.2- [3- (3-piperidinomethyl) phenoxy) propyl] -5-amino-pyrimidin-4-one or a pharmaceutically acceptable salt. 2-[3-(3-피페리디노메틸)페녹시)프로필아미노]-5-아세트아미도피리미딘-4-온 혹은 약제학상허용 가능한 염.2- [3- (3-piperidinomethyl) phenoxy) propylamino] -5-acetamidopyrimidin-4-one or a pharmaceutically acceptable salt. 2-[3-(3-피페리디노메틸)페녹시)프로필아미노]-5-아미노-피리미딘-4-온 혹은 약제학상허용 가능한 염.2- [3- (3-piperidinomethyl) phenoxy) propylamino] -5-amino-pyrimidin-4-one or a pharmaceutically acceptable salt. 2-[3-(4-피페리디노메틸)피리드-2-옥시)프로필아미노]-5-아미노피리미딘-4-온 혹은 약제학상허용 가능한 염.2- [3- (4-piperidinomethyl) pyrid-2-oxy) propylamino] -5-aminopyrimidin-4-one or a pharmaceutically acceptable salt. 2-[3-(4-피페리디노메틸)피리드-2-옥시)프로필]-5-아미노피리미딘-4-온 혹은 약제학상허용 가능한 염.2- [3- (4-piperidinomethyl) pyrid-2-oxy) propyl] -5-aminopyrimidin-4-one or a pharmaceutically acceptable salt. 2-[3-[3-(헥사하이드로 아제피노메닐)페녹시]프로필아미노]-5-아미노피리미딘-4-온 혹은 약제학상허용 가능한 염 및 2-[3-[3-피페리디노메틸)페녹시프로필]-5-아미노]-6-메틸피리미딘-4-온 혹은 약제학상허용 가능한 염을 제조하는 청구범위 제1항에 따른 방법.2- [3- [3- (hexahydro azenomenyl) phenoxy] propylamino] -5-aminopyrimidin-4-one or a pharmaceutically acceptable salt and 2- [3- [3-piperidinomethyl ) Phenoxypropyl] -5-amino] -6-methylpyrimidin-4-one or a method according to claim 1 for preparing a pharmaceutically acceptable salt. 2-[3-(3-피페리디노메틸)페녹시)프로필]-5-아미노피리미딘-4-온 혹은 약제학상허용 가능한 염을 제조하는 청구범위 제1항에 따른 방법.A process according to claim 1 for preparing 2- [3- (3-piperidinomethyl) phenoxy) propyl] -5-aminopyrimidin-4-one or a pharmaceutically acceptable salt. R0,m,y,p,q 및 R3가 청구범위 제1항에서 정의된 바와같은 일반식(XVI)의 화합물이나 이들의 염을 환원하는 것으로 구성되는 R4가 수소인 청구범위 제1항에서 정의된 바와같은 일반식(1)의 화합물(1)이나 이들의 염을 제조하는 방법.Claim 1 wherein R 4 , consisting of reducing compounds of formula (XVI) or salts thereof, wherein R 0 , m, y, p, q and R 3 are as defined in claim 1 A process for preparing compound (1) of formula (1) or salts thereof as defined in the paragraph. 2-[3-(3-피페리디노메틸)페녹시-프로필]-5-니트로피리미딘-4-온을 환원하는 것으로 구성되는 2-[3-(3-피페리디노-메틸)페녹시)프로필-5-아미노피리미딘-4-온을 제조하는 방법.2- [3- (3-piperidino-methyl) phenoxy consisting of reducing 2- [3- (3-piperidinomethyl) phenoxy-propyl] -5-nitropyrimidin-4-one C) propyl-5-aminopyrimidin-4-one. 환원제가 충분한 중성조건하에 염화제일 주석으로 구성되는 청구범위 제11항이나 제12항에 따른 방법.The process according to claims 11 or 12, wherein the reducing agent consists of tin tin chloride under sufficient neutral conditions. 용매가 에틸아세테이트로 구성되고 염화제일주석이 무수형태인 청구범위 제13항에 따른 방법.The process according to claim 13, wherein the solvent consists of ethyl acetate and the stannous chloride is in anhydrous form. 청구범위 제1항에서 정의된 바와같은 일반식(1)의 화합물이나 이들의 약제학상허용 가능한 염 및 약학상허용 가능한 담체를 연합하는 것으로 구성되는 약제학적 조성물을 제조하는 방법.A process for preparing a pharmaceutical composition comprising associating a compound of formula (1) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier as defined in claim 1. 일반식(1)의 화합물이 2-[3-(3-피페리디노메틸)-페녹시)프로필]-5-아미노피리미딘-4-온인 청구범위 제15항에 따른 방법.The process according to claim 15, wherein the compound of formula (1) is 2- [3- (3-piperidinomethyl) -phenoxy) propyl] -5-aminopyrimidin-4-one. 일반식(XVI)의 화합물이나 이들의 염.Compounds of general formula (XVI) and salts thereof. 여기에서,From here, R0는 2-구아니디노티아졸-4-일이나 R1R2N(CH2)n-Z-이고, R1과 R2은 독립적으로 수소, C1-6알킬, 아릴(C1-6) 알킬, 헤테로아릴(C1-6) 알킬, C3-10싸이클로알킬, 하이드록시(C2-6) 알킬, 혹은 할로(C2-6) 알킬(여기에서 상기 하이드록시와 할로그룹은 질소원소에 인접한 탄소원자에서 치환되지 않는다)이거나; R1과 R2는 다같이 q가 5-8원 포화합을 붙게하는 질소원자와 함께 형성되게끔 q가 4-7인 (CH2)q을 나타내고, n은 1-6의 정수이며; Z는 R1R2N(CH2)n그룹이 4-위치에 있는 2,5-푸라닐, 2,5-티에틸, 2,4-피리딜이거나, R1R2N(CH2)n그룹이 2-위치에 있는 2,4-티아졸릴 혹은 1,3이나 1,4-페닐렌이고; m은 1이거나; z가 피리딜이나 페닐렌이면 m은 0일수도 있고; Y는 산소, 유황이나 메틸렌이거나, 혹은 Z는 푸라닐이나 티에닐, 티아졸릴이면, Y는 또한 단일 결합일수도 있고; P는 2,3-이나 4이고; q는 0이나 1이고; R3는 수소나 C1-6알킬이다.R 0 is 2-guanidinothiazol-4-yl or R 1 R 2 N (CH 2 ) n -Z-, and R 1 and R 2 are independently hydrogen, C 1-6 alkyl, aryl (C 1 -6 ) alkyl, heteroaryl (C 1-6 ) alkyl, C 3-10 cycloalkyl, hydroxy (C 2-6 ) alkyl, or halo (C 2-6 ) alkyl, wherein the hydroxy and halo groups Is not substituted at a carbon atom adjacent to a nitrogen element); R 1 and R 2 together represent (CH 2 ) q, where q is 4-7, so that q is formed with a nitrogen atom to attach a 5-8 membered saturated sum, n is an integer from 1-6; Z is 2,5-furanyl, 2,5-thiethyl, 2,4-pyridyl, wherein the R 1 R 2 N (CH 2 ) n group is in the 4-position, or R 1 R 2 N (CH 2 ) the n group is 2,4-thiazolyl in the 2-position or 1,3 or 1,4-phenylene; m is 1; m may be 0 if z is pyridyl or phenylene; If Y is oxygen, sulfur or methylene, or Z is furanyl, thienyl, thiazolyl, Y may also be a single bond; P is 2,3- or 4; q is 0 or 1; R 3 is hydrogen or C 1-6 alkyl. 2-[3-(3-피페리디노메틸)페녹시)프로필]-5-니트로피리미딘-4-온.2- [3- (3-piperidinomethyl) phenoxy) propyl] -5-nitropyrimidin-4-one. 다음에 관한 것을 포함하는 청구범위 제17항에서 정의된 바와같은 일반식(XVI)의 화합물을 제조하는 방법.A process for preparing a compound of formula (XVI) as defined in claim 17 comprising: (a) 일반식(II)의 화합물을 m,y,p 및 R3가 청구범위 제1항에서 정의된 바와같고, R6가 청구범위 제1항에서 정의된 바와 같은 R0그룹이거나 R6가 푸란-2-일이나 티엔-2-일그룹이며; Q가 아민으로 치환가능한 그룹인 일반식(IIIA)의 화합물과 반응시키는, q가 1인 일반식(XVI)의 화합물에 관한 것이나;(a) a compound of formula (II) wherein m, y, p and R 3 are as defined in claim 1 and R 6 is a R 0 group as defined in claim 1 or R 6 Is furan-2-yl or thien-2-yl group; To a compound of the general formula (XVI) wherein q is 1, wherein Q is reacted with a compound of the general formula (IIIA) wherein the group is substituted with an amine; R6(CH2)m-Y-(CH2)pNHZ R 6 (CH 2 ) m -Y- (CH 2 ) p NH Z (II)(II) (b) 일반식(IV)의 화합물을, R6,p,q 및 R3가 청구범위 제1항에서 정의된 바와같고 L이 티올이나 이들의 화학적 등가물로 일부 치환가능한 일반식(VA)의 화합물과 반응시키는 m이 1이고 Y가 유황인 일반식(XVI)의 화합물에 관한 것이나;(b) a compound of formula (IV) wherein R 6 , p, q and R 3 are as defined in claim 1 and L is partially substituted by thiol or a chemical equivalent thereof A compound of formula (XVI) wherein m is 1 and Y is sulfur to react with the compound; R6-CH2-L (IV) R 6 -CH 2 -L (IV) (c) 일반식(VI)의 화합물이나 이들의 화학적 등가물을, R6,p,q 및 R3가 청구범위 제1항에서 정의된 바와같고, L1이 티올이나 이들의 화학적 등가물에 의해 일부 치환가능한 일반식(XIIA)의 화합물과 반응시키는; m이 1이고, Y가 유황인 일반식(XVI)의 화합물에 관한 것이나;(c) Compounds of formula (VI) and their chemical equivalents, wherein R 6 , p, q and R 3 are as defined in claim 1 and L 1 is partially substituted by thiols or their chemical equivalents. Reacting with a compound of substitutable general formula (XIIA); m relates to compounds of formula (XVI) wherein m is 1 and Y is sulfur; R6CH2SH (VI) R 6 CH 2 SH (VI) (d) 일반식(VIII)의 화합물을, R6,m,y,p,q 및 R3가 청구범위 제1항에서 정의된 바와 같고, R7이 에스텔 형성그룹인 일반식(IXB)의 화합물이나 이들의 화학적 등가물과 반응시키는 것에 관한 것이나;(d) a compound of formula (VIII) wherein R 6 , m, y, p, q and R 3 are as defined in claim 1 and R 7 is an ester forming group; To react with compounds or their chemical equivalents; (e) 일반식(X)의 화합물을, R1,R2,n,p,q 및 R3가 청구범위 제1항에서 정의된 바와같고 L2가 하이드록시나 이들의 등가물에 의해서 치환가능한 그룹인 일반식(XIA)이나 반응을 일으킬수 있는 이들의 유도체와 반응시키는, z가 2,4-피리딜이고, m이 0이며 y가 산소인 일반식(XVI)의 화합물에 관한 것; 또는(e) a compound of formula (X) wherein R 1 , R 2 , n, p, q and R 3 are as defined in claim 1 and L 2 is displaceable by hydroxy or an equivalent thereof; To a compound of the general formula (XVI) wherein z is 2,4-pyridyl, m is 0 and y is oxygen, which is reacted with a general formula (XIA) which is a group or derivatives thereof which can cause a reaction; or (f) 일반식(XII)의 화합물이나 이들의 화학적 등가물을, R1,R2,n,p,q 및 R3가 청구범위 제1항에서 정의된 바와 같고 L3가 페놀이나 이들의 화학적 등가물로 일부치환 가능한 일반식(XIIIA)의 화합물과 반응시키는 z가 페닐렌이고, m이 0이며 Y가 산소인 일반식(XVI)의 화합물에 관한 것이나;(f) Compounds of the general formula (XII) and their chemical equivalents, wherein R 1 , R 2 , n, p, q and R 3 are as defined in claim 1 and L 3 is phenol or their chemical Z relates to a compound of formula (XVI) wherein z is phenylene, m is 0 and Y is oxygen, which is reacted with a compound of formula (XIIIA) which is partially substituted by an equivalent; (g) z,m,y,p,q 및 R3가 청구범위 제1항에서 정의된 바와같고 R8가 청구범위 제1항에서 정의된 바와같은 R1R2N(CH2)n-그룹의 전개물인 일반식(XIVA)의 화합물을 전환하는, R0가 R1R2N(CH2)n-z-인 일반식(XVI)의 화합물에 관한 것이나;(g) R 1 R 2 N (CH 2 ) n − as z, m, y, p, q and R 3 are as defined in claim 1 and R 8 is as defined in claim 1 To a compound of formula (XVI) wherein R 0 is R 1 R 2 N (CH 2 ) n -z-, which converts a compound of formula (XIVA) which is a development of the group; (h) m,y,p 및 R3가 청구범위 제1항에서 정의된 바와같고 R9이 R0그룹이거나 청구범위 제1항에서 정의된 바와같은 R8-z-이며, R10이 -CH=N-이나 -CO-NH인 일반식(XVA)의 화합물을 환원하는, q가 1인 일반식(XVI)의 화합물에 관한 것과 그후에 필요시에는;(h) m, y, p and R 3 are as defined in claim 1 and R 9 is a group R 0 or R 8 -z- as defined in claim 1 and R 10 is-. For compounds of formula (XVI) wherein q is 1 which reduces the compound of formula (XVA) with CH═N— or —CO—NH; (i) R6가 푸란-2-일이나 티엔-2-일인 화합물은 만니히시약과 반응시켜 n이 1인 일반식(XVI)의 화합물을 형성하는 것; (ii) 임의로 염을 형성하는 것.(i) a compound wherein R 6 is furan-2-yl or thien-2-yl is reacted with Mannich reagent to form a compound of formula (XVI) wherein n is 1; (ii) optionally forming a salt. 4-[3-(피페리디노메틸)페녹시]부티론 아미딘과 일반식(IXB)의 화합물이나 청구범위 제19항에서 정의된 바와같은 이들의 화학적 등가물을 반응시키는 것으로 구성되는 2-[3-(3피페리디노-메틸)페녹시)프로필]-5-니트로피리미딘-4-온을 제조하는 방법.2- [consisting of reacting 4- [3- (piperidinomethyl) phenoxy] butyron amidine with a compound of formula (IXB) or their chemical equivalents as defined in claim 19 3- (3piperidino-methyl) phenoxy) propyl] -5-nitropyrimidin-4-one. 일반식(IXB)의 화합물이나 이들의 화학적 등가물이, R7이 에스텔형성그룹이고 X가 치환가능한 그룹인 일반식;The compound of formula (IXB) and chemical equivalents thereof are those in which R 7 is an ester forming group and X is a substitutable group; 일반식의 화합물인 청구범위 제20항에 따른 방법.The method according to claim 20, which is a compound of the general formula. R7이 C1-6알킬이고, X가 C1-6알콕시인 청구범위 제21항에 따른 방법.The method according to claim 21, wherein R 7 is C 1-6 alkyl and X is C 1-6 alkoxy. ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.※ Note: The disclosure is based on the initial application.
KR1019840004474A 1983-07-29 1984-07-27 Chemical compound KR850001174A (en)

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US4772704A (en) * 1983-09-21 1988-09-20 Bristol-Myers Company 2,5-disubstituted-4(3H)-pyrimidones having histamine H2 -receptor antagonist activity
GB8421427D0 (en) * 1984-08-23 1984-09-26 Smith Kline French Lab Chemical compounds
JP2007531753A (en) 2004-03-31 2007-11-08 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ Non-imidazole heterocyclic compounds
AU2007256931B2 (en) 2006-05-30 2013-01-24 Janssen Pharmaceutica N.V. Substituted pyridyl amide compounds as modulators of the histamine H3 receptor
KR101546712B1 (en) 2007-11-20 2015-08-24 얀센 파마슈티카 엔.브이. Cycloalkyloxy- and heterocycloalky-loxypyridine compounds as modulators of the histamine h3 receptor
WO2022034121A1 (en) 2020-08-11 2022-02-17 Université De Strasbourg H2 blockers targeting liver macrophages for the prevention and treatment of liver disease and cancer

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IN151188B (en) * 1978-02-13 1983-03-05 Smith Kline French Lab
ZA793443B (en) * 1978-07-26 1980-12-31 Glaxo Group Ltd Heterocyclic derivatives
US4496567A (en) * 1978-11-13 1985-01-29 Smith Kline & French Laboratories Limited Phenyl alkylaminopyrimidones
US4521418A (en) * 1979-02-21 1985-06-04 Smith Kline & French Laboratories Limited Guanidinothiazolyl derivatives
ZW21281A1 (en) * 1980-10-01 1981-11-18 Smith Kline French Lab Amine derivatives
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CS581084A2 (en) 1985-08-15
FI842976A (en) 1985-01-30
DE3476541D1 (en) 1989-03-09
ES8600254A1 (en) 1985-09-16
PT78977B (en) 1986-06-05
EP0134096B1 (en) 1989-02-01
GB8320505D0 (en) 1983-09-01
GR82226B (en) 1984-12-13
EP0134096A2 (en) 1985-03-13
FI842976A0 (en) 1984-07-26
ES534620A0 (en) 1985-09-16
ZW11584A1 (en) 1985-04-17
IL72491A0 (en) 1984-11-30
ZA845820B (en) 1985-06-26
DK368284D0 (en) 1984-07-27
JO1327B1 (en) 1986-11-30
EP0134096A3 (en) 1985-12-18
AU564650B2 (en) 1987-08-20
HUT34743A (en) 1985-04-28
ATE40552T1 (en) 1989-02-15
CS244448B2 (en) 1986-07-17
AU3099184A (en) 1985-01-31
DD216933A5 (en) 1985-01-02
PT78977A (en) 1984-08-01
CA1261831A (en) 1989-09-26
NO843043L (en) 1985-01-30
DK368284A (en) 1985-01-30
JPS6051179A (en) 1985-03-22

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